Field of the Disclosure
This disclosure generally relates to apparatus and methods for filtering a fluid, such as but not limited to a biological fluid. More particularly, this disclosure relates to apparatus and methods for filtering a biological fluid, such as blood that includes the removal of leukocytes from whole blood or a blood component. The disclosure further relates to systems and methods that allow for automated air management, filtration and recovery of blood or blood components.
Description of Related Art
Prior to transfusion of blood or a blood component into a recipient, it is common to filter the blood product to remove leukocytes. This process is commonly referred to as leukoreduction. It may be desirable to remove leukocytes from blood or a blood component prior to transfusion because they can trigger a broad range of graft-versus-host adverse reactions in a recipient, ranging from minor effects, such as chills, to more serious effects, such as the transmission of cytomegalovirus, which can be fatal to recipients with weakened immune systems.
Commonly, blood processing with leukoreduction involves the transfer of blood or a blood component from a pre-filter fluid container to a post-filter fluid container through a tubing line having a leukoreduction filter. The filter and tubing line typically include a quantity of air or gas (non-liquid and non-solid), generally referred to hereafter as “air”, that is pushed out of the tubing and filter upon priming the same during a filtration application. It is desired to prevent this air from moving into the post-filter container and remaining there, because such air aggregation can prevent complete filtration of the blood, as will be described in greater detail herein, and decrease the quality and storability of the filtered blood. Even when the blood or blood component is used a short time after filtration, there is a general preference among users to have as little air in the post-filter container as possible.
Known approaches to air management include filtration systems that are vented to the atmosphere or an air container and those incorporating a bypass line. For example, U.S. Pat. No. 5,863,436 to Matkovich, which is hereby incorporated herein by reference, describes several leukoreduction systems incorporating one or more air vents. One commercial system according to the description of Matkovich is the Pall SAVE™ system, which is incorporated into the Leukotrap® WB Filtration System from Pall Corporation of Glen Cove, N.Y. The Leukotrap® WB Filtration System comprises a pre-filter container connected to a post-filter container by a filter line having a leukoreduction filter. A pre-filter air vent is associated with the filter line between the pre-filter container and the filter, while a post-filter air vent is associated with the filter line between the filter and the post-filter container. In use, the pre-filter container is hung above the post-filter container and a cannula of the pre-filter container is broken to allow fluid flow into the filter line. The fluid is prevented from flowing into the pre-filter air vent by a removable cap, so it instead flows into the filter. The filter is allowed to prime, with air exiting the system through the post-filter air vent. When the filter is fully primed, a cannula between the post-filter vent and the post-filter container is broken to allow fluid and air to flow into the post-filter container. Due to pressure differentials in the system, the filtration process ceases prior to complete filtration of all the fluid, i.e., with an amount of fluid remaining in the filter. At that time, the cap on the pre-filter air vent is removed to allow air to enter the filter line and purge any remaining fluid from the inlet side of the filter.
One problem with systems according to the foregoing description is that no means are provided to remove air from the post-filter container, either during or after filtration. While the post-filter vent removes the air that is purged from the filter, air may be initially present in the system at other locations, such as in the containers or the tubing, as a result of the manufacturing process. This air is pushed into the post-filter container during filtration and can lead to the aforementioned diminished performance and quality concerns if not removed during or after filtration.
In response to the foregoing problem, leukoreduction systems incorporating bypass lines allow removal of air from the post-filter container during and/or after filtration. Several examples of known leukoreduction systems with bypass lines are described in U.S. Pat. No. 6,358,420 to Blickhan et al., which is hereby incorporated herein by reference. In one system, a pre-filter container is connected to a post-filter container by a filter line having a leukoreduction filter. Tubing providing a bypass line is connected to the filter line at opposite sides of the filter, thereby allowing for fluid communication between the containers along a path that bypasses the filter. The bypass line is provided with a one-way valve, typically a check valve, which only allows air and fluid flow toward the pre-filter container from the post-filter container. In use, the pre-filter container is hung above the post-filter container and a cannula of the pre-filter container is broken to allow fluid flow into the filter line. The fluid is prevented from flowing through the bypass line and into the post-filter container by the one-way valve. The fluid flows through the filter and into the post-filter container, along with an amount of air. Due to pressure differentials in the system, the filtration process ceases prior to complete filtration of the fluid, i.e., with an amount of fluid remaining in the filter. At that time, a slide clamp is placed on the filter line, between the filter and the post-filter container, and the post-filter container is squeezed to force air through the bypass line and toward the pre-filter container. Squeezing the post-filter container to remove air is sometimes referred to as “burping” the container. When the post-filter container has been “burped,” the clamp is removed from the filter line and the filter is allowed to more completely drain.
According to another leukoreduction system described in Blickhan et al., one end of the bypass line is connected to the filter line at a position between the pre-filter container and the filter, while the other end is connected directly to the post-filter container. This system operates similarly to the previously described system of Blickhan et al. to filter blood or a blood component and remove air from the post-filter container.
While systems incorporating bypass lines represent improvements over the systems of Matkovich in terms of air removal from the post-filter container, the need to manually “burp” the container to remove air may be problematic. In particular, the amount of air removal is directly dependent on the strength and skill of the user, which can potentially lead to insufficient or incomplete air removal. In addition, the effort required by the operator in terms of having to bend down or kneel to reach the post-filter container and then having to apply a squeezing force with both hands is undesirable, and can lead to operator fatigue, error and lower quality results.
A more recent approach to eliminating the manual “burping” step is to allow for automatic “burping” of the post-filter container. Several such systems are described in U.S. Pat. No. 6,171,493 to Zia et al., which is hereby incorporated herein by reference. Rather than connecting the bypass line to one or more sections of the filter line, one end of the bypass line is directly connected to the pre-filter container and the other end of the bypass line is directly connected to the post-filter container. The pre-filter container is hung above the post-filter container and, in one embodiment, a loop portion of the filter line is elevated above the fluid level in the pre-filter container to prevent fluid from flowing through the bypass line and into the post-filter container. A clamp on the filter line is opened to allow fluid flow through the filter line and the filter. Air in the filter is pushed into the post-filter container by the blood and begins to accumulate therein and/or to leak from the post-filter container into the bypass line. When the pressure in the post-filter container reaches a sufficient level and the pressure in the pre-filter container decreases sufficiently (typically to a vacuum state), some of the air moves up the bypass line, through the loop portion, and into the pre-filter container. The return of air to the pre-filter container increases the pressure above the filter and assists in more completely draining any remaining fluid from the filter.
In theory, the “burping” system of Zia et al. improves on previously known systems by automatically removing air from the post-filter container, without requiring a manual “burping” operation. However, the efficiency of the Zia et al. system is contingent on the pressure differential between the post-filter container and the pre-filter container. Optimal filtration results are achieved when pressure in the post-filter container is maximized. If only a small amount of fluid is to be filtered, then the post-filter container will remain relatively empty and the pressure developed therein will not be sufficient to re-circulate the air to the pre-filter container. In such situations, the post-filter container must be manually squeezed to remove air, thereby representing a failure of the intended automatic “burping” feature.
There are systems which use a different method referred to as retro-priming. In transfusion medicine, this concept is used in red blood cell filtration where before filtration by gravity starts, the post-filter container contains a solution such as Ad-Sol and the pre-filter container contains packed red blood cells. This method may be used by gravity, such as by initially suspending the post-filter container at a height above the other components, or manually such as by squeezing the post-filter container to force the fluid up through the post-filter container, post-filter flow path, and filter until the air in these portions of the system is forced upward toward and/or into the pre-filter container that contains the fluid to be filtered. Depending on the volume of each component in the system, the retro-priming may be continued to additionally force the air to continue to flow upward through the pre-filter flow path and to all be deposited into the pre-filter container, along with some of the solution from the post-filter container. This method has proven successful in evacuating air from a system, but includes the drawback of extra time required, as well as requiring intervention and manual effort by an operator to affect the changes in height or squeezing of the components.
Even more recent air management systems and methods are described in U.S. patent application Ser. No. 11/618,286, which is hereby incorporated herein by reference. The systems in this application incorporate gravity-based filtration, but include apparatus that is adapted to limit an amount of air in the post-filter container during and after filtration of a biological fluid by reducing the maximum volume of the post-filter container, and by using a bypass line to assist in air removal. A post-filter container normally would be expandable to a maximum volume that may be equal to or exceed the volume of the pre-filter container. However, by use of a smaller post-filter container or use of a restrictor or volume restriction device, such as for example a band around the post-filter container, or locating the post-filter container between a pair of plates, the maximum capacity of the post-filter container can be reduced. The restriction on the growth of the post-filter container tends to increase the effectiveness of the transmission of air through the bypass line and ultimately improves the recovery of fluid through the filter, as disclosed in the application.
Another separate problem with the foregoing systems is that they merely utilize gravity to move the fluid during the filtration process. The rate of gravity filtration can vary widely and is dependent on the density of the fluid being filtered, the temperature, the inner diameter of the tubing used in the system, the relative heights of the pre-filter container, post-filter container and any of the intermediate components, such as the filter. The force of gravity is a constant, nevertheless, gravity filtrations can range in time from tens of minutes to a few hours. Thus, not only is the amount of time objectionable, but the unpredictability of the time required to complete the process is bothersome and inconvenient to operators and for scheduling purposes.
While some of the systems described above have worked satisfactorily, there remains a need for apparatus and methods for more efficiently filtering fluid products with respect to the amount and predictability of the time required to complete the process, as well as with respect to the removal of air from a post-filter container, and with less dependence on the amount of fluid to be filtered.